Pharmaceutical compositions containing water soluble drugs are well known in the pharmaceutical arts. For example venlafaxine, 1-[2-dimethylamaino-1-(4-methoxyphenyl)ethyl]cyclohexanol, a drug used for treatment of depression is currently being sold in tablet form. In addition, U.S. Pat. Nos. 6,274,171 and 6,403,120, both to Sherman, et al. describe an extended release formulation of venlafaxine hydrochloride in capsule form. As described therein, the venlafaxine hydrochloride is mixed with a formulation aid, such as microcrystalline cellulose and hydroxypropylmethylcellulose and the plastic mass thus formed is extruded, spheronized and dried to provide uncoated spheroids containing the drug. The spheroids are coated with controlled release polymers, such as hydroxypropylmethyl cellulose, in order to provide a controlled release formulation.
This procedure described in the aforementioned patents requires several steps. For example, it requires wet granulation to make a wet mass for extrusion, the mass is then passed through an extruder to make cylindrical rods of proper diameter, and then the rods are then spheronized using a spheronizer to make spheres. The resulting spheres are then dried, sized and coated with the controlled release polymer to obtain a controlled release formulation.
This process described therein has several disadvantages:
First, it requires several steps and is thus labor intensive; the steps, are at a minimum wet granulation, extrusion, spheronization, drying, sizing and coating.
Second, this methodology often does not produce spheres with uniform diameters, which thus may result in lower process yields.
Third, the process requires a formulation aid such as microcrystalline cellulose and hydroxyproplmethyl cellulose, for spheronization, consequently, it is not difficult to prepare beads and/or capsules containing beads having high concentrations of drug thereon.
Fourth, since the process requires a wet granulation step, it may require non-aqueous solvents, such as ethanol which can be hazardous as well as expensive.
The present inventor, however, has found a much simpler and much more efficient method of making pharmaceutical compositions containing venlafaxine hydrochloride and other water soluble drugs which does not require all of the steps described hereinabove.
The present inventor has found that he can eliminate the wet granulation step, the extrusion step and spheronization steps of the prior art by utilizing a supersaturated solution of the water soluble drug with or without other components and coating inert beads with same. If a controlled release formulation is required, the controlled release polymer is contained in a second coating which is coated onto the first coating comprising the water soluble drug and other components, wherein said first coating coats the inert beads.
Another common way to make a pharmaceutical in which the drug is coated onto a bead or pellet is to disperse the drug in a solvent containing a binder dissolved therein and to coat the inert bead with this solution. A fluidized bed coating method is commonly used to effect this type of coating. To effect coating of the beads with the drug, the drug precipitates or crystallizes out of the solution as the solvent is removed. If the drug does not precipitate out of the solution, it forms a very sticky coating which makes drug loading almost impossible. The presence of a binder, which provides binding and/or stickiness, only worsens the situation. Moreover, if the drug is highly water soluble, the drug does not easily precipitate out of solution. Thus, heretofore no one has extended the use of this methodology for coating water soluble drugs on a bead or pellet.
However, the present inventor has overcome this problem and found a way to coat pellets by modifying this method.